Overview
For patients with advanced non-small cell lung cancer (NSCLC) and high PD-L1 expression (≥50%) who lack standard targetable mutations, immunotherapy is the primary first-line treatment. However, patients often also carry other genetic mutations (such as KEAP1, STK11, KRAS, and TP53) that currently lack approved targeted therapies. This study used the Flatiron Health-Foundation Medicine NSCLC Clinico-Genomic Database (CGDB) to analyze 1,240 patients with these mutations. Researchers found that while some of these mutations (KEAP-1 and STK11) trended toward lower response rates, they were not statistically associated with worse survival or time to progression. Instead, baseline demographic and clinical factors, such as older age and poor physical function, remained the main drivers of patient outcomes.
Why this matters
Using combined clinical and genomic real-world data, this study elucidates the impact of common genetic mutations in patients with high PD-L1 NSCLC. The findings suggests that current immunotherapies remain active despite these mutations, while simultaneously highlighting a crucial unmet need for improved risk-stratification tools and novel, targeted therapies for these high-risk patient subgroups.